Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are two types of perfluorinated compounds (PFCs) frequently studied in recent years due to their potential for bioaccumulation and toxicity to humans. Usually, PFCs can co-exist in various environment. Therefore, over- or under-estimated risk assessments would result if antagonism or synergism occurred in mixture toxicity. In the present study, the acute and chronic toxicities of single and mixtures of PFOA and PFOS to Daphnia magna were investigated. PFOS was more toxic than PFOA, both in 48-h acute toxicity and 21-d chronic toxicity. In acute toxicity tests, mixture toxicities showed strong synergistic effects on mortality. The experimental EC50 of the mixture is 4.44 × 10-5 mol/L, whereas the predicted EC50 is 8.19 × 10-5 mol/L by Concentration Addition Model and 9.73 × 10-5 mol/L by Independent Action Model. In chronic toxicity tests, synergistic effects were also found in the aspects of offspring. The offspring rate is reduced significantly to 39.8% at the 9.61 × 10-7 mol/L of mixture, while, PFOS and PFOA do not have effects when they are tested individually at corresponding concentrations. To explore the potential mechanism of the synergistic effect, the interactions between PFCs and proteins, including acetylcholinesterase, superoxide dismutase, catalase, ecdysone receptor and glutathione-S-transferase, were investigated by the Molecular Docking. The docking results revealed that the driving forces for the binding of PFCs with proteins were predominantly hydrophobic and hydrogen-bonding interactions. Based on the binding models, we deduced that the potential mechanism of synergism is that PFOS and PFOA have similar binding modes with catalase and have different binding modes with superoxide dismutase. Overall, these data provide experimental evidence that there is strong synergism in acute and chronic toxicity of mixtures to D. magna and demonstrate that molecular structure of some components of the antioxidant defence system contributes to the synergistic interaction.
Keywords: Antioxidant system; Molecular modeling; Protein-ligand complex; Synergistic toxicity; Water flea.
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